The pathogenesis of autoimmunity in New Zealand mice is still uncertain; however, advances are being made. The disease has a genetic and immune basis; however, expression of severity can be modified by viral and other environmental factors as well as sex hormones. The immunologic factors are complex. These include excessive B-cell activation and impaired T-cell suppressive activity. The loss of T-cell activity is related to a deficiency of suppressor cell precursors. Antibodies to T-cells produce an accelerated loss of suppressor cells and their precursors. Excessive B-cell activation can be modified by introducing the X chromosome of a CBA/N mouse into the NZB autoimmune background. The CBA/N X chromosome which codes for defects in B-cell maturation causes a reduction in autoimmunity in F1 mice, and in preliminary experiments in congenic mice. Male sex hormones present in the first few weeks of life markedly retard anti-DNA production later in life.